A 26-year-old woman with a history of polycystic ovarian syndrome presented with secondary amenorrhea, worsening hirsutism, acne, deepening of voice and unexplained 10-20 kg weight gain. Her Ferriman-Gallway hirsutism score was 12 with cystic facial acne and increased masculine phenotype. Urine Beta-Human Chorionic Gonadotropins (bHCG) was negative. She had elevated serum testosterone of 551 ng/dL, androstenedione at 7.46 ng/mL and dehydroepiandrosterone sulfate (DHEAS) at 4243 µg/L. Overnight dexamethasone suppression test showed mildly unsuppressed cortisol (2.89 µg/dL). Urinary free cortisol along with paired serum cortisol and adrenocorticotrophic hormone (ACTH) tests were normal (55.4 µg/24 hours, 13.44 mcg/dL, 30.4 pg/mL respectively). Her leutinizing hormone (LH) was low(<0.1 mIU/mL), follicle stimulating hormone (FSH) low/normal (1.41 mIU/mL) with sex hormone binding globulin (SHBG) level 45nmol/L and the rest of the pituitary and adrenal workup was unremarkable. Thyroid stimulating hormone (TSH) was 2.15mU/mL. MRI revealed a 3.1 cm, indeterminate but well-defined left adrenal lesion and polycystic ovaries without abdominal lymphadenopathy. Given radiological appearances and despite biochemical concerns for adrenocortical malignancy, a multidisciplinary team meeting decision was made to proceed with laparoscopic adrenalectomy. Histology was consistent with a benign adenoma. Postoperatively, there was clinical and biochemical resolution of the disease.
Mammary gland development requires hormonal regulation during puberty, pregnancy, and lactation. Brominated flame retardants (BFRs) are endocrine disruptors; they are added to consumer products to satisfy flammability standards. Previously, we showed that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts proteins of the adherens junctions in rat dam mammary glands at weaning. Here, we hypothesize that perinatal exposure to the same BFR mixture also disrupts junctional proteins and signaling pathways controlling mammary gland development in pups. Dams were exposed through diet to a BFR mixture based on the substances in house dust; doses of the mixture used were 0, 0.06, 20, or 60 mg/kg/day. Dams were exposed continuously beginning prior to mating until pups’ weaning; female offspring were euthanized on postnatal day (PND) 21, 46, and 208. The lowest dose of BFRs significantly downregulated adherens junction proteins, E-cadherin, and β-catenin, and the gap junction protein p-Cx43, as well as thyroid hormone receptor alpha 1 protein at PND 46. No effects were observed on estrogen or progesterone receptors. The low dose also resulted in a decrease in cleaved caspase-3, a downward trend in PARP levels, proteins involved in apoptosis, and an upward trend in proliferating cell nuclear antigen, a marker of proliferation. No effects were observed on ductal elongation or on the numbers of terminal end buds. Together, our results indicate that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts cell-cell interactions, thyroid hormone homeostasis and the proliferation-apoptosis balance at PND 46, a critical stage for mammary gland development.
Objectives: Female individuals with BRCA1 germline mutation have an 80-90% risk to develop breast cancer during their lifetime. BRCA1 cancers are distinct from sporadic breast cancers as they more frequently show high-grade histology and are typically estrogen receptor and HER2-negative. While sporadic breast ductal carcinoma is thought to be preceded by in-situ precursors, the presence of precursors is uncertain in BRCA1 cancers. To better understand breast carcinogenesis in BRCA1 patients, we developed an approach to perform unprecedently detailed structural analysis of breast tissue. Design: A prophylactic mastectomy product of a BRCA1 patient with history of contralateral breast cancer was obtained after routine pathological evaluation then trimmed into 0.3 × 1 x1.5 cm tissue blocks (n=94). Initial sections from each block were H&E stained and microscopically evaluated. Any lobular or ductal structure with increased cellularity was recorded as hyperplastic event. Correlation of hyperplastic events on the surface of blocks and topographic information of events led to the identification of “hot” regions with larger numbers of these events. From the center of this region, the block was serially sectioned at 5μm-depth. H&E staining of every tenth section allowed a three-dimensional (3D) reconstruction of all hyperplastic events. The same procedure was applied to a normal control tissue product of a prophylactic mastectomy in a non-BRCA1 patient with personal history of contralateral breast cancer. Results: We identified five novel “isolated epithelial structures” within BRAC1 breast tissue. On a single two dimensional (2D) slide, these isolated epithelial structures resemble regular lobular and ductal structures with hyperplastic features; while after 3D reconstruction with 2D slides, they revealed in isolation from connection to regular anatomic epithelial structures and were entirely separated by mesenchymal tissue. Importantly, we report in detail an isolated tubular epithelial structure in association with an incidental millimeter-sized, BRCA1-deficient cancer focus. This structure is 2mm in length, mostly surrounded by myoepithelial cells, and remarkable for simultaneous development of lobular and ductal hyperplasia including flat epithelial hyperplasia. The transition zone into cancer is characterized by loss of myoepithelial cells and significant cytologic atypia. Conclusions: Our thorough examination of BRCA1 breast tissue allowed for the first time the identification of isolated epithelial structures. Our identification of one isolated epithelial structure in connection with the development of an infiltrating carcinoma focus strongly suggests that isolated epithelial structures are potential precursors for BRCA1 breast cancers. Analysis of these structures may lead to the discovery of new preventive and therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 224. doi:10.1158/1538-7445.AM2011-224
CASEA 54-year-old man with a 3-month history of pain and swelling on the left side of his jaw and 1-day history of left eye droop was transferred to the ED from the state psychiatric hospital. Four weeks ago, he had a dental abscess treated with doxycycline and clindamycin, but the abscess did not improve. His history also is signifi cant for alcohol abuse and Wernicke-Korsakoff syndrome. He reported a 10-to 15-lb (4.5 to 6.8 kg) weight loss over the past few months, night sweats, headaches, and orthostatic hypotension but was unable to fully communicate due to his jaw pain. The cognitive limitations caused by WernickeKorsakoff syndrome also interfered with his ability to be an accurate historian.Physical examination The patient was alert and oriented with stable vital signs. Examination of the fi fth cranial nerve revealed a sensory defect of all three branches on the left side of his face and a right tilted uvula. His extraocular muscles were intact and his pupils were equal, round, and reactive to light and accommodation. The remaining cranial nerves were not examined. A retinal examination was negative for papilledema. He had decreased strength (3/5) in the bilateral trapezius muscles; all other muscle strength testing was 5/5. He had 2+ refl exes and a negative Babinski sign. Lymphadenopathy was noted in the left anterior cervical chain. CT of the head and neck with and without contrast were ordered in the ED, and the patient was admitted to the neurology telemetry unit and was later transferred to hospice care.Diagnostic testing Head and neck CT scan without contrast (Figure 1) was negative for fractures, cranial masses, or herniation. The CT was positive only for thickening of the maxillary sinuses consistent with chronic sinusitis. When a head and neck CT scan with contrast (Figure 2) was done, a 4.1x2.5x5.4 cm mass was found in the patient's left nasopharynx at the left skull base. The mass was seen eroding into the cervical spine at C1 and C2. No infl ammatory changes surrounded the mass but multiple enlarged lymph nodes were noted. The lack of infl ammation adjacent to the lesion in addition to the local aggressiveness of the mass and anatomic location led to a diagnosis of nasopharyngeal carcinoma. When the patient was informed of his diagnosis and the treatment plans, he refused all treatment. A capacity consult was placed and he was determined to be incapable of making any decisions about his medical treatment. He
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.